Tumor necrosis factor alpha (TNFα), a mononuclear cytokine, is predominately produced by monocytes and macrophages. It possesses various biological activities: (1) killing cancer cells or inhibiting growth of cancer cells, (2) enhancing the phagocytosis of neutrophilic granulocytes, (3) up-regulating the production of peroxide, and (4) killing infection pathogens.
Interleukin-1 beta (IL-1β), a cytokine secreted by cells such as monocyte macrophages and dendritic cells, mediates immune and inflammatory responses.
Nuclear factor-kappa B (NF-κB) is a pro-inflammatory transcription factor. It upregulates cytokines, including TNFα and IL-1β, and thereby mediates the inflammatory response.
Inducible nitric oxide synthase (iNOS) is induced by endotoxins or cytokines (e.g., TNFα). It catalyzes the production of nitric oxide, an important pleiotropic molecule, from L-aginine and oxygen.
TNFα, IL-1β, NF-κB, and iNOS play important roles in many key physiological and pathological processes relating to a wide range of diseases, e.g., autoimmune diseases, cancer, atherosclerosis, and diabetes. Therefore, modulating the expression or activity of TNFα, IL-1β, NF-κB, or iNOS can lead to treatment of these diseases. See, e.g., Ogata H, Hibi T. et al Curr Pharm Des. 2003; 9(14): 1107-13; Taylor P C. et al Curr Pharm Des. 2003; 9(14): 1095-106; Fan C., et al. J. Mol. Med 1999,. 77, 577-592; and Alcaraz et al., Current Pharmaceutical Design, 2002: 8, 215.